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A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory tract illness. Its higher transmission and infecti...

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Autores principales: Anand, Nithishwer Mouroug, Liya, Devang Haresh, Pradhan, Arpit Kumar, Tayal, Nitish, Bansal, Abhinav, Donakonda, Sainitin, Jainarayanan, Ashwin Kumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971693/
https://www.ncbi.nlm.nih.gov/pubmed/33735271
http://dx.doi.org/10.1371/journal.pone.0248553
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author Anand, Nithishwer Mouroug
Liya, Devang Haresh
Pradhan, Arpit Kumar
Tayal, Nitish
Bansal, Abhinav
Donakonda, Sainitin
Jainarayanan, Ashwin Kumar
author_facet Anand, Nithishwer Mouroug
Liya, Devang Haresh
Pradhan, Arpit Kumar
Tayal, Nitish
Bansal, Abhinav
Donakonda, Sainitin
Jainarayanan, Ashwin Kumar
author_sort Anand, Nithishwer Mouroug
collection PubMed
description The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory tract illness. Its higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. One of the major concerns involving the SARS-COV-2 is the mutation rate, which enhances the virus evolution and genome variability, thereby making the design of therapeutics difficult. In this study, we identified the most common haplotypes from the haplotype network. The conserved genes and population level variants were analysed. Non-Structural Protein 10 (NSP10), Nucleoprotein, Papain-like protease (Plpro or NSP3) and 3-Chymotrypsin like protease (3CLpro or NSP5), which were conserved at the highest threshold, were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs, which are suggested for further pre-clinical and clinical trials. This particular study provides a comprehensive targeting of the conserved genes. We also identified the mutation frequencies across the viral genome.
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spelling pubmed-79716932021-03-31 A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing Anand, Nithishwer Mouroug Liya, Devang Haresh Pradhan, Arpit Kumar Tayal, Nitish Bansal, Abhinav Donakonda, Sainitin Jainarayanan, Ashwin Kumar PLoS One Research Article The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory tract illness. Its higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. One of the major concerns involving the SARS-COV-2 is the mutation rate, which enhances the virus evolution and genome variability, thereby making the design of therapeutics difficult. In this study, we identified the most common haplotypes from the haplotype network. The conserved genes and population level variants were analysed. Non-Structural Protein 10 (NSP10), Nucleoprotein, Papain-like protease (Plpro or NSP3) and 3-Chymotrypsin like protease (3CLpro or NSP5), which were conserved at the highest threshold, were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs, which are suggested for further pre-clinical and clinical trials. This particular study provides a comprehensive targeting of the conserved genes. We also identified the mutation frequencies across the viral genome. Public Library of Science 2021-03-18 /pmc/articles/PMC7971693/ /pubmed/33735271 http://dx.doi.org/10.1371/journal.pone.0248553 Text en © 2021 Anand et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Anand, Nithishwer Mouroug
Liya, Devang Haresh
Pradhan, Arpit Kumar
Tayal, Nitish
Bansal, Abhinav
Donakonda, Sainitin
Jainarayanan, Ashwin Kumar
A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing
title A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing
title_full A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing
title_fullStr A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing
title_full_unstemmed A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing
title_short A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing
title_sort comprehensive sars-cov-2 genomic analysis identifies potential targets for drug repurposing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971693/
https://www.ncbi.nlm.nih.gov/pubmed/33735271
http://dx.doi.org/10.1371/journal.pone.0248553
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